Stimulation of the mesencephalic locomotor region (MLR) is known to initiate and maintain walking in the brainstem-transected animal by modulating locomotion oscillators present in the spinal cord. Over the past several years we have applied clsssical neurophysiological and anatomical methods in the locomotion on a treadmill preparation. Our studies have demonstrated the presence of projections from the two main outputs of the basal ganglia, the pallidum and substantia nigra (SN), to the MLR Recent findings revealed the occurrence in MLR neurons, of rhythmic firing patterns related to locomotor movements. These studies established that the pedunculopontine necleus, a known termination sitse of basal ganglia outputs, forms part of the MLR. In addition, the overall anatomical organization of other afferents and of the efferents of the MLR were described in the walking preparation. Significantly, we reported that descending MLR efferents travel via Probst's tract and to the nucleus reticularis gigantocellularis (NRG), a source of reticulospinal projections. Our latest findings provide a significant advance in the application of this preparation, not only as a model for the study of locomotion, but also as a method for investigating chemotherapeutic strategies in the treatment of diseases involving locomotor movements, e.g. Parkinsonism, stroke, trauma. The limitations of stimulation-induced locomotion (fatigability, variability and low yield) now can readily be overcome with the use of chemical-induced locomotion. We have been able to induce locomotion by application of pharmacological substances within the MLR. Our preliminary findings suggest that chemical-induced locomotion is, 1) site specific, i.e. produces locomotion only when application is made within the MLR, 2) transmitter specific, and 3) provides lasting, reproducible walking. The proposed research will take advantage of this development in order to investigate, 1) the chronology and characteristics of rhythms present in MLR, NRG and SN neurons during chemical-induced locomotion, 2) the ability of NRG to induce, or modulate MLR-induced, locomotion, and 3) the ability of the SN to modulate MLR- or NRG-induced locomotion. These studies will provide comprehensive information which should enable the design of an appropriate chemotherapeutic and/or prosthetic control for locomotor events - the ultimate aim of this research.